Marshall-Smith syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: MRSHSS
Accelerated skeletal maturation - peculiar facies - failure to thrive
Number of Symptoms 98
OrphanetNr: 561
OMIM Id: 602535
ICD-10: Q87.3
UMLs: C0265211
MeSH: C536026
MedDRA:
Snomed: 73284007

Prevalence, inheritance and age of onset:

Prevalence: 33 cases [Orphanet]
Inheritance: Unknown
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic multiple congenital anomalies/dysmorphic syndrome - variable intellectual deficit
 -Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome - variable intellectual deficit
 -Rare developmental defect during embryogenesis
Overgrowth syndrome
 -Rare developmental defect during embryogenesis
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000978) Bruising susceptibility Frequent [Orphanet] 123 / 7739
2
 (HPO:0000316) Hypertelorism Frequent [Orphanet] 644 / 7739
3
 (HPO:0000520) Proptosis Very frequent [Orphanet] 192 / 7739
4
 (HPO:0000586) Shallow orbits 23 / 7739
5
 (HPO:0000592) Blue sclerae Frequent [Orphanet] 85 / 7739
6
 (HPO:0002092) Pulmonary hypertension 109 / 7739
7
 (HPO:0002093) Respiratory insufficiency Very frequent [Orphanet] 410 / 7739
8
 (HPO:0011951) Aspiration pneumonia 6 / 7739
9
 (HPO:0002100) Recurrent aspiration pneumonia 6 / 7739
10
 (HPO:0001601) Laryngomalacia Frequent [Orphanet] 61 / 7739
11
 (HPO:0000098) Tall stature 74 / 7739
12
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 492 / 7739
13
 (HPO:0001508) Failure to thrive 454 / 7739
14
 (HPO:0030680) Abnormality of cardiovascular system morphology Occasional [Orphanet] 355 / 7739
15
 (HPO:0001631) Atria septal defect 274 / 7739
16
 (HPO:0002119) Ventriculomegaly Occasional [Orphanet] 253 / 7739
17
 (HPO:0001643) Patent ductus arteriosus 228 / 7739
18
 (HPO:0000158) Macroglossia Frequent [Orphanet] 119 / 7739
19
 (HPO:0001252) Muscular hypotonia 990 / 7739
20
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
21
 (HPO:0010547) Muscle flaccidity 466 / 7739
22
 (HPO:0001324) Muscle weakness 859 / 7739
23
 (HPO:0001249) Intellectual disability 1089 / 7739
24
 (HPO:0001270) Motor delay 322 / 7739
25
 (HPO:0002870) Obstructive sleep apnea 16 / 7739
26
 (HPO:0006487) Bowing of the long bones Very frequent [Orphanet] 95 / 7739
27
 (HPO:0009882) Short distal phalanx of finger 125 / 7739
28
 (HPO:0009845) Bullet-shaped middle phalanges of the hand 1 / 7739
29
 (HPO:0006048) Distal widening of metacarpals 1 / 7739
30
 (HPO:0000277) Abnormality of the mandible Very frequent [Orphanet] 394 / 7739
31
 (HPO:0000347) Micrognathia 426 / 7739
32
 (HPO:0003778) Short mandibular rami 7 / 7739
33
 (HPO:0000278) Retrognathia 100 / 7739
34
 (HPO:0010759) Prominence of the premaxilla 5 / 7739
35
 (HPO:0001363) Craniosynostosis Occasional [Orphanet] 132 / 7739
36
 (HPO:0002007) Frontal bossing Very frequent [Orphanet] 366 / 7739
37
 (HPO:0011220) Prominent forehead 137 / 7739
38
 (HPO:0006642) Large sternal ossification centers 1 / 7739
39
 (HPO:0000879) Short sternum 16 / 7739
40
 (HPO:0000767) Pectus excavatum 244 / 7739
41
 (HPO:0003311) Hypoplasia of the odontoid process 34 / 7739
42
 (HPO:0003414) Atlantoaxial dislocation 5 / 7739
43
 (HPO:0002650) Scoliosis Frequent [Orphanet] 705 / 7739
44
 (HPO:0003416) Spinal canal stenosis 28 / 7739
45
 (HPO:0001274) Agenesis of corpus callosum 142 / 7739
46
 (HPO:0004349) Reduced bone mineral density Frequent [Orphanet] 165 / 7739
47
 (HPO:0001382) Joint hypermobility Very frequent [Orphanet] 231 / 7739
48
 (HPO:0003100) Slender long bone Very frequent [Orphanet] 45 / 7739
49
 (HPO:0002652) Skeletal dysplasia Very frequent [Orphanet] 113 / 7739
50
 (HPO:0005616) Accelerated skeletal maturation Very frequent [Orphanet] 46 / 7739
51
 (HPO:0002659) Increased susceptibility to fractures Frequent [Orphanet] 110 / 7739
52
 (HPO:0011362) Abnormal hair quantity Frequent [Orphanet] 92 / 7739
53
 (HPO:0000664) Synophrys 112 / 7739
54
 (HPO:0000574) Thick eyebrow 96 / 7739
55
 (HPO:0000998) Hypertrichosis 52 / 7739
56
 (HPO:0001537) Umbilical hernia 206 / 7739
57
 (HPO:0001539) Omphalocele 102 / 7739
58
 (HPO:0000272) Malar flattening 277 / 7739
59
 (HPO:0011800) Midface retrusion 221 / 7739
60
 (HPO:0000168) Abnormality of the gingiva Occasional [Orphanet] 51 / 7739
61
 (HPO:0000212) Gingival overgrowth 43 / 7739
62
 (HPO:0000162) Glossoptosis 26 / 7739
63
 (HPO:0000194) Open mouth Frequent [Orphanet] 70 / 7739
64
 (HPO:0000322) Short philtrum 130 / 7739
65
 (HPO:0000463) Anteverted nares Very frequent [Orphanet] 305 / 7739
66
 (HPO:0000453) Choanal atresia Occasional [Orphanet] 76 / 7739
67
 (HPO:0000452) Choanal stenosis 23 / 7739
68
 (HPO:0005280) Depressed nasal bridge Very frequent [Orphanet] 381 / 7739
69
 (HPO:0003196) Short nose Frequent [Orphanet] 264 / 7739
70
 (HPO:0000405) Conductive hearing impairment Frequent [Orphanet] 164 / 7739
71
 (HPO:0000369) Low-set ears 372 / 7739
72
 (HPO:0000396) Overfolded helix 21 / 7739
73
 (HPO:0002104) Apnea 106 / 7739
74
 (HPO:0000974) Hyperextensible skin Very frequent [Orphanet] 59 / 7739
75
 (HPO:0000963) Thin skin Very frequent [Orphanet] 96 / 7739
76
 (HPO:0000365) Hearing impairment 539 / 7739
77
 (HPO:0002334) Abnormality of the cerebellar vermis Occasional [Orphanet] 137 / 7739
78
 (HPO:0012795) Abnormality of the optic disc Occasional [Orphanet] 187 / 7739
79
 (HPO:0000006) Autosomal dominant inheritance 2518 / 7739
80
 (HPO:0002059) Cerebral atrophy 171 / 7739
81
 (HPO:0011420) Death Frequent [Orphanet] 184 / 7739
82
 (HPO:0003819) Death in childhood 42 / 7739
83
 (HPO:0001522) Death in infancy Frequent [Orphanet] 275 / 7739
84
 (HPO:0040079) Irregular dentition 7 / 7739
85
 (HPO:0007227) Macrogyria 9 / 7739
86
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
87
 (HPO:0003745) Sporadic 131 / 7739
88
 (OMIM) Bullet-shaped middle phalanges 1 / 7739
89
 (OMIM) Early death 13 / 7739
90
 (OMIM) Everted lips 3 / 7739
91
 (OMIM) Irregular dentition 6 / 7739
92
 (OMIM) Long cranium 1 / 7739
93
 (OMIM) Narrowed distal phalanges 1 / 7739
94
 (OMIM) Prominent frontal bone 1 / 7739
95
 (OMIM) Proximal and middle phalanges 1 / 7739
96
 (OMIM) Rudimentary epiglottis 1 / 7739
97
 (OMIM) Thick clavicles 1 / 7739
98
 (OMIM) Underweight for length 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) The Marshall-Smith syndrome is a malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia (Adam et al., ...
Clinical Description OMIM Marshall et al. (1971) described 2 infants with a syndrome characterized by accelerated skeletal maturation, failure to thrive, and dysmorphic facial features. Sperli et al. (1993) reviewed 20 reported cases.

Chatel et al. (1998) reported an ...
Molecular genetics OMIM Based on an Nfix-deficient mouse model with a phenotype similar to that in Marshall-Smith syndrome, Malan et al. (2010) screened 9 individuals with MRSHSS for NFIX mutations and found heterozygosity for 7 independent frameshift mutations (164005.0002-164005.0008) and 2 ...